Age-related brain pathologies caused by neurodegeneration (ND), such as Alzheimer's disease (AD) and Parkinson's disease (PD), affect millions world-wide each year. Such brain pathologies are often mediated by reactive oxygen species primarily originating from mitochondria (mROS). However, although oxidative stress and mROS play a role in ND pathogenesis, this knowledge has not led to the development of an effective treatment. For example, targeting a known antioxidant (MitoQ) specifically to quench mROS has failed (Murphy, et al., Ann. Rev. Pharmacol. Toxicol. 47:629-656 (2007); Snow, et al., Mov. Disord. 25:1670-1674 (2010); Tauskela, Drugs 10:399-412 (2007); Lloret, et al., J. Alzheimer's Disease. [Epub ahead of print, PMID: 21876249 (2011)). Moreover traditional antioxidants α-tocopherol, ascorbate and α-lipoate, although safe, have been ineffective in treating AD patients (Lott, et al., Amer. J. Med. Genet. 155:1939-1948 (2011)). This can be partially explained by the fact that mROS normally perform several physiological functions of vital importance, and their total elimination entails death of the organism. For example, mice and rats kept in a chamber with O2-free air die within three weeks (Goldstein, Biochemistry (Mosc) 67:161-170 (2002)).
Thus, there remains a great need for treatments for ND pathologies.
Previously, in US Patent Application Publication US 2011/0053895 (“the '895 application”), we described how mitochondria-targeted rechargeable antioxidants can be used for the prevention and treatment of cardiovascular pathologies as well as diseases and pathological conditions originating from disorders of blood circulation or oxygen supply to tissues and organs. The '895 application includes examples that show that pretreatment with SkQR1 can provide a prophylactic effect against brain hemorrhagic stroke and behavioral abnormalities caused by cerebral compression ischemia. However, to date, there has been nothing that would show or suggest a prophylactic effect of mitochondria-targeted rechargeable antioxidants against other brain pathologies or an effect in the treatment of brain pathologies generally.